Rodent Neural Progenitor Cells Support Functional Recovery after Cervical Spinal Cord Contusion

被引:18
作者
Brock, John Hoffman [1 ,2 ]
Graham, Lori [2 ]
Staufenberg, Eileen [2 ]
Im, Sarah [2 ]
Tuszynski, Mark Henry [1 ,2 ]
机构
[1] VA San Diego Healthcare Syst, San Diego, CA USA
[2] Univ Calif San Diego, La Jolla, CA 92093 USA
关键词
functional recovery; neural progenitor cells; spinal cord cervical contusion; STEM-CELLS; AXONAL GROWTH; INJURY; TRANSPLANTS; CONNECTIVITY; RECEPTORS; PROTEIN;
D O I
10.1089/neu.2017.5244
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Previously, we and others have shown that rodent neural progenitor cells (NPCs) can support functional recovery after cervical and thoracic transection injuries. To extend these observations to a more clinically relevant model of spinal cord injury, we performed unilateral midcervical contusion injuries in Fischer 344 rats. Two-weeks later, E14-derived syngeneic spinal cord-derived multi-potent NPCs were implanted into the lesion cavity. Control animals received either no grafts or fibroblast grafts. The NPCs differentiated into all three neural lineages (neurons, astrocytes, oligodendrocytes) and robustly extended axons into the host spinal cord caudal and rostral to the lesion. Graft-derived axons grew into host gray matter and expressed synaptic proteins in juxtaposition with host neurons. Animals that received NPC grafts exhibited significant recovery of forelimb motor function compared with the two control groups (analysis of variance p<0.05). Thus, NPC grafts improve forelimb motor outcomes after clinically relevant cervical contusion injury. These benefits are observed when grafts are placed two weeks after injury, a time point that is more clinically practical than acute interventions, allowing time for patients to stabilize medically, simplifying enrollment in clinical trials, and enhancing predictability of spontaneous improvement in control groups.
引用
收藏
页码:1069 / 1078
页数:10
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